Roles of Cellular Neighborhoods in Hepatocellular Carcinoma Pathogenesis

Annu Rev Pathol. 2025 Jan;20(1):169-192. doi: 10.1146/annurev-pathmechdis-111523-023520.

Abstract

The development of hepatocellular carcinoma (HCC) involves an intricate interplay among various cell types within the liver. Unraveling the orchestration of these cells, particularly in the context of various etiologies, may hold the key to deciphering the underlying mechanisms of this complex disease. The advancement of single-cell and spatial technologies has revolutionized our ability to determine cellular neighborhoods and understand their crucial roles in disease pathogenesis. In this review, we highlight the current research landscape on cellular neighborhoods in chronic liver disease and HCC, as well as the emerging computational approaches applicable to delineate disease-associated cellular neighborhoods, which may offer insights into the molecular mechanisms underlying HCC pathogenesis and pave the way for effective disease interventions.

Keywords: HCC; MASH; cellular neighborhoods; hepatocellular carcinoma; immune microenvironment; metabolic dysfunction–associated steatohepatitis; spatial transcriptome.

Publication types

  • Review

MeSH terms

  • Animals
  • Carcinoma, Hepatocellular* / etiology
  • Carcinoma, Hepatocellular* / genetics
  • Carcinoma, Hepatocellular* / pathology
  • Humans
  • Liver / metabolism
  • Liver / pathology
  • Liver Neoplasms* / etiology
  • Liver Neoplasms* / genetics
  • Liver Neoplasms* / pathology
  • Tumor Microenvironment